MONONINE 1000 IU POWDER AND SOLVENT FOR SOLUTION FOR INJECTION OR INFUSION

Transcript

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• If a central venous access device is required, a risk of catheter-related complications
including local infections, bacteraemia and catheter-site thrombosis should be
considered.
• There is no safety and efficacy data for continuous infusion application in children,
particularly the potential for development of inhibitors is unknown.
Your doctor will consider carefully the benefit of treatment with Mononine compared with
the risk of these complications.

Package leaflet: Information for the user

Mononine® 1000 IU
powder and solvent for solution for injection or infusion
Human coagulation factor IX
Read all of this leaflet carefully before you start using this medicine,
because it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may
harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side
effects not listed in this leaflet.
In this leaflet:
1. What Mononine is and what it is used for
2. What you need to know before you use Mononine
3. How to use Mononine
4. Possible side effects
5. How to store Mononine
6. Contents of the pack and other information

Virus safety
When medicines are made from human blood or plasma, certain measures are put in
place to prevent infections being passed on to patients. These include:
– careful selection of blood and plasma donors to make sure those at risk of carrying
infections are excluded,
– the testing of each donation and pools of plasma for signs of virus/infections,
– the inclusion of steps in the processing of the blood or plasma that can inactivate or
remove viruses.
Despite these measures, when medicines prepared from human blood or plasma are
administered, the possibility of passing on infection cannot be totally excluded. This also
applies to any unknown or emerging viruses or other types of infections.
The measures taken are considered effective for enveloped viruses such as human
immunodeficiency virus (HIV, the aids virus), hepatitis B virus and hepatitis C virus
(inflammation of the liver) and for the non-enveloped hepatitis A and parvovirus B19
viruses.
Your doctor may recommend that you consider vaccination against hepatitis A and B if
you regularly/repeatedly receive human plasma-derived products (e.g. factor IX).
It is strongly recommended that every time Mononine is given, you should record the date
of administration, the batch number and the injected volume in your treatment diary.

What is Mononine?
Mononine is made from human plasma (this is the liquid part of the blood) and it contains
human coagulation factor IX. It is used to prevent or to stop bleeding that is caused by
the congenital lack of factor IX (haemophilia B) in the blood.

Other medicines and Mononine
• Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines.
• Factor IX and ε-aminocaproic acid (a chemical drug that stops the breakdown of blood
clots) can be used to treat bleeding from the mouth, either if this happens after injury
or after dental surgery, such as having teeth removed. However, there is not very much
information about what happens when ε-aminocaproic acid and Mononine are given
at the same time.
• Mononine must not be mixed with other medicinal products, diluents and solvents
except for those that are recommended by the manufacturer (see section 6).

What Mononine is used for
Factor IX is very important for blood clotting (coagulation). Lack of factor IX means that
blood does not clot as quickly as it should and so there is an increased tendency to bleed.
The replacement of factor IX with Mononine will temporarily repair the blood clotting
mechanisms.
The made up solution is to be given by injection or infusion into a vein.

Pregnancy, breast-feeding and fertility
• If you are pregnant or breast-feeding, think you may be pregnant or are planning to
have a baby, ask your doctor or pharmacist for advice before taking this medicine.
• During pregnancy and breast-feeding, Mononine should be given only if it is clearly
needed.
• No fertility data are available.

2. What you need to know before you use Mononine

Driving and using machines
Mononine has no influence on the ability to drive and use machines.

1. What Mononine is and what it is used for

The following sections contain information that you and your doctor should consider
before you use Mononine.
Do not use Mononine:
• If you are allergic to the human coagulation factor IX or any of the other ingredients
of this medicine (listed in section 6.1) or to mouse protein. Please inform your doctor
if you are allergic to any medicine or food.
• If you have a high risk of forming blood clots (thrombosis) or if you are more likely to
form blood clots than normal (disseminated intravascular coagulation).
Warnings and precautions
• Allergic reactions are possible. The early signs include hives, generalised skin rash, tightness
of the chest, wheezing, fall in blood pressure and anaphylaxis (a serious allergic reaction
that causes severe difficulty in breathing, or dizziness).
If these symptoms occur, you should stop using the product immediately
and contact your doctor.
• Mononine contains, as remains of a special purification step, traces of mouse
protein. While the levels of mouse protein are extremely low, infusion of these proteins
can lead to allergic reactions.
• The formation of inhibitors (neutralising antibodies) to factor IX is a known complication
of treatment and it means that the treatment stops working. If your bleeding is not
being controlled with Mononine, tell your doctor immediately. You should be monitored
carefully for the development of an inhibitor.
• There is a risk of an increased formation of blood clots in a blood vessel (thromboembolic complications), particularly:
 if you suffer from a liver disease
 if you have just had surgery
 in new-born infants
 if you have additional thrombotic risk factors, e.g. pregnancy, oral contraceptives,
obesity, smoking.
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Important information about some of the ingredients in Mononine
A standard dose of 2000 IU Mononine contains up to 30.36 mg sodium. Please take this
into account if you are on a controlled sodium diet.

• Any unused product or waste material should be disposed of in accordance with local
requirements and as instructed by your doctor.

Reconstitution:
Without opening either vial, warm the Mononine product and the solvent to room or body
temperature. This can be done either by leaving the vials at room temperature for about
an hour, or by holding them in your hands for a few minutes.
DO NOT expose the vials to direct heat. The vials must not be heated above body
temperature (37 ºC).
Carefully remove the protective caps from the vials containing the product and the solvent,
and clean the exposed rubber stoppers with an alcohol swab. Allow the vials to dry before
opening the Mix2Vial package, then follow the instructions given below.
1. Open the Mix2Vial package by peeling off the lid. Do not
remove the Mix2Vial from the blister package!

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2. Place the solvent vial on an even, clean surface and hold the
vial tight. Take the Mix2Vial together with the blister package
and push the spike of the blue adapter end straight down
through the solvent vial stopper.

3. Carefully remove the blister package from the Mix2Vial set by
holding at the rim, and pulling vertically upwards. Make sure
that you only pull away the blister package and not the
Mix2Vial set.

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On demand treatment
The calculation of the required dose of factor IX is based on the empirical finding that
1 IU factor IX per kg body weight raises the plasma factor IX activity by 1.0 % of normal
activity.
The required dosage is determined using the following formula:
Required units = body weight [kg] × desired factor IX rise [% or IU/dl] × 1.0
The amount to be administered, the method as well as the frequency of administration
should always be oriented to the clinical effectiveness in the individual case.
In the case of the following haemorrhagic events, the factor IX activity should not fall
below the given plasma activity level (in % of normal or IU/dl) in the corresponding period.
The following tables can be used to guide dosing in bleeding episodes and surgery:
Table 1: SINGLE INTRAVENOUS INJECTION

Early haemarthrosis,
muscle bleeding or
oral bleeding

20 – 40

Repeat every 24 hours. At least
1 day, until the bleeding episode
as indicated by pain is resolved
or healing is achieved.

More extensive
haemarthrosis, muscle
bleeding or haematoma

30 – 60

Repeat infusion every 24 hours
for 3 – 4 days or more until pain
and acute disability are resolved

Life-threatening
haemorrhages

60 – 100

Repeat infusion every 8 to 24
hours until threat is resolved.

30 – 60

Every 24 hours, at least 1 day,
until healing is achieved

Surgery
4. Place the product vial on an even and firm surface. Invert the
solvent vial with the Mix2Vial set attached and push the spike
of the transparent adapter end straight down through the
product vial stopper. The solvent will automatically flow into
the product vial.

Minor
including tooth extraction
Major

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5. With one hand grasp the product-side of the Mix2Vial set and
with the other hand grasp the solvent-side and unscrew the
set carefully counter-clockwise into two pieces. Discard the
solvent vial with the blue Mix2Vial adapter attached.

Duration of treatment
6. Gently swirl the product vial with the transparent adapter
attached until the substance is fully dissolved. Do not shake.

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7. Draw air into an empty, sterile syringe. While the product vial
is upright, connect the syringe to the Mix2Vial´s Luer Lock
fitting by screwing clockwise. Inject air into the product vial.

80 – 100
Repeat infusion every
(pre- and postoperative) 8 – 24 hours until adequate
wound healing, then therapy for
at least another 7 days to
maintain a factor IX activity of
30 % to 60 % (IU/dl)

Table 2: CONTINUOUS INFUSION IN SURGERY

Frequency of dosing

Reconstitution and application

General instructions:
• The product must be dissolved and withdrawn from the vial under aseptic conditions.
• The made up solution should be clear or slightly opalescent, i.e. it might be sparkling
when held up to the light but must not contain any obvious particles.
After filtering or withdrawal (see below) the solution should be checked by eye for
small particles and discoloration, before it is administered. Do not use the solution if it
is visibly cloudy or if it contains flakes or particles.
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One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX
in one ml of normal human plasma.

Haemorrhage

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Dosage
The amount of factor IX you need and the duration of treatment will depend on several
factors, such as your body weight, the severity of your disease, the site and intensity of
the bleeding or the need to prevent bleeding during an operation or investigation.
If you have been prescribed Mononine to use at home, your doctor will make sure that
you are shown how to inject or infuse it and how much to use.
Follow the directions given to you by your doctor or haemophilia centre nurse.
If you take more Mononine than you should
No symptoms of overdose with factor IX have been reported.

Posology
The number of units of factor IX administered is expressed in International Units (IU),
which are related to the current WHO standard for factor IX products. Factor IX activity
in plasma is expressed either as a percentage (relative to normal human plasma) or in
International Units (relative to an International Standard for factor IX in plasma).

3. How to use Mononine
Always use this medicine exactly as your doctor has told you. Check with your doctor or
pharmacist if you are not sure.
Treatment of Haemophilia B should be started and supervised by a physician who is
experienced in this type of disorder.

The following information is intended for healthcare professionals only

Prophylaxis
For long-term prophylaxis against bleeding in patients with severe haemophilia B, the
usual doses are 20 to 40 IU of factor IX per kg body weight at intervals of 3 to 4 days. In
some cases, especially in younger patients, shorter dosage intervals or higher doses may
be necessary.
During the course of treatment, appropriate determination of factor IX levels is advised
to guide the dose to be administered and the frequency of repeated infusions. In the case
of major surgical interventions in particular, precise monitoring of the substitution therapy
by means of coagulation analysis (plasma factor IX activity) is indispensable. Individual
patients may vary in their response to factor IX, achieving different levels of in vivo recovery
and demonstrating different half-lives.
Patients should be monitored for the development of factor IX inhibitors.

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Previously untreated patients
The safety and efficacy of Mononine in previously untreated patients have not yet been
established.
Paediatric population
Dosing in children is based on body weight and is therefore generally based on the same
guidelines as for adults. The frequency of administration should always be oriented to the
clinical effectiveness in the individual case.
Application
Mononine could be administered either by single intravenous injection (see instructions
in section 3) or by continuous infusion (see instructions below).
Continuous infusion
Mononine should be reconstituted with water for injections as described in section
”Reconstitution and application”. After reconstitution, Mononine can be given for
continuous infusion either undiluted or diluted using a syringe pump or an approved
infusion set.
The potency of undiluted, reconstituted Mononine is approximately 100 IU/ml.
A diluted solution is obtained as follows:
• Dilute the reconstituted, filtered solution by transferring the appropriate quantity of
Mononine to the desired volume of normal saline using aseptic technique.
• In dilutions of up to 1:10 (concentration of 10 IU factor IX/ml) activity of factor IX
remains stable for up to 24 hours.
• A reduction in factor IX activity may result at higher dilutions. Factor IX activity should
be monitored to maintain the desired blood level.
Example for diluting 1000 IU of reconstituted Mononine:
Targeted Dilution Potency

10 IU/ml

20 IU/ml

Volume of reconstituted Mononine

10.0 ml

10.0 ml

Volume of normal saline needed

90.0 ml

40.0 ml

1:10

1:5

Achieved dilution

• The use of polyvinylchloride (PVC) IV bags and tubing is recommended.
• Mix thoroughly and check bag for leaks.
• It is recommended to replace the bags with freshly diluted Mononine every
12 – 24 hours.
The recommended rate for continuous infusion with Mononine to maintain a steady state
factor IX level of approximately 80 % is 4 IU/kg b.w./hour, but will depend on the
pharmacokinetic profile of the patient and the desired factor IX target level. In patients
where the clearance of factor IX is known, the infusion rate can be calculated for the
individual patient.
Rate (IU/kg b.w./h) = Clearance (ml/h/kg b.w.) × desired factor IX increase (IU/ml)
The safety and efficacy in children have not been studied under continuous infusion.
Therefore, in children and adolescents, continuous infusion of Mononine should only be
considered if pre-surgical pharmacokinetic data (i.e. incremental recovery and clearance) are
obtained for the calculation of dosage and levels are carefully monitored perioperatively.

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Withdrawal and application:
8. While keeping the syringe plunger pressed, invert the system
upside down and draw the solution into the syringe by pulling
the plunger back slowly.

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9. Now that the solution has been transferred into the syringe,
firmly hold on to the barrel of the syringe (keeping the syringe
plunger facing down) and disconnect the transparent Mix2Vial
adapter from the syringe by unscrewing counter-clockwise.

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Single intravenous injection
Use the venipuncture kit that is supplied with the product, insert the needle into a vein.
Let blood flow back to the end of the tube. Attach the syringe to the threaded, locking
end of the venipuncture kit. Inject the made up solution slowly into the vein
following the instructions given to you by your doctor. Take care not to get any blood in
the syringe containing the made up solution. The maximum rate of administration is
2 millilitres per minute.
Continuous infusion
Mononine can also be given by a long-term (continuous) infusion over several hours or
days. This must be done and controlled by your doctor.
Check yourself for any side effects that might happen straight away. If you have any side
effects that might be related to the administration of Mononine, the injection or infusion
should be stopped (see also section “Warnings and precautions”).
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following happen, contact your doctor immediately or go to the
Emergency Department or Haemophilia Centre at your nearest hospital:
• A sudden allergic reaction (such as skin rash or hives, itchiness, swelling of the face,
lips, tongue or other parts of the body)
• Shortness of breath, wheezing or trouble breathing
• Fits
• Loss of effect (continuous bleeding)
Other side effects are:
• Allergic reactions, which may include:
 burning and stinging, redness and swelling of the vein where the injection or infusion
was given
 swelling of the face or throat or other parts of the body, chills, flushing, skin rash
over the whole body, wheals
 headache
 fall in blood pressure, restlessness, faster heart-beat, tightness of the chest, wheezing
 tiredness (lethargy)
 feeling/being sick
 tingling
These side effects have been observed rarely, and may in some cases progress to
severe allergic reactions (anaphylaxis) including shock (this has been closely associated
with development of factor IX inhibitors).
• Rarely, fever has been reported.
• Very rarely, a special form of inflammation of the kidneys (nephrotic syndrome) has
been reported after treatment of patients who suffer from factor IX inhibitors. These
patients were also known to have a history of allergic reaction.
• There is a potential risk of increased formation of blood clots that can lead to heart
attack (myocardial infarction), blood clots in the leg (venous thrombosis) and blood
clots in the lungs (pulmonary embolism), after administration of factor IX products. The
use of Mononine is rarely linked with these side effects.
• Very rarely, you may develop an inhibitor (neutralising antibody) to factor IX, in which
case factor IX will not work properly any more. If this happens, it is recommended that
a specialised haemophilia centre be contacted.

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Side effects in children and adolescents
The frequency, type and severity of adverse reactions in children are expected to be the
same as in adults.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible
side effects not listed in this leaflet. You can also report side effects directly via the
UK MHRA Yellow Card scheme. Website: www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide more information of the safety of this
medicine.
5. How to store Mononine
Do not use Mononine after the expiry date, which is stated on the label and carton.
• Keep this medicine out of the sight and reach of children.
• Do not freeze.
• Keep the vial in the outer carton in order to protect from light.
• Store in a refrigerator (2 ºC – 8 ºC).
• During its shelf life the product (when kept in its outer carton) may be stored at ambient
room temperature (up to 25 ºC) for up to one month without being refrigerated again
during this period. The date of transfer to room temperature and the end of the
1-month period should be recorded on the outer carton. At the end of the period, the
product has to be used or discarded.
• The made up solution should be used immediately.
• If the made up solution is diluted (up to one part in 10), the solution must be used
immediately, however the physico-chemical stability has been demonstrated for 24 hours.
• Your doctor will inform you how to dispose of unused product or waste material.
6. Contents of the pack and other information
What Mononine contains
Mononine contains 1000 IU human coagulation factor IX per vial.
Once dissolved with 10 ml (1000 IU) of the solvent, the made up solution contains
approximately 100 IU human coagulation factor IX per ml.
Other ingredients are:
Histidine, mannitol, sodium chloride, hydrochloric acid or sodium hydroxide (in small
amounts for pH adjustment)
Solvent: Water for injections
What Mononine looks like and contents of the pack
Mononine is presented as a white powder and is supplied with water for injections as
solvent.
The made up solution should be clear to slightly opalescent, i.e. it might sparkle when
held up to the light but must not contain any obvious particles.
Presentation
One pack with 1000 IU containing:
– 1 vial with powder
– 1 vial with 10 ml water for injections
One device pack containing:
– 1 filter transfer device 20/20
– 1 disposable 10 ml syringe
– 1 venipuncture set
– 2 alcohol swabs
– 1 non-sterile plaster
Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
This leaflet was last revised in 11/2014.

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.